Therapies for preventing or suppressing Clostridium difficile infection

Abstract

The present invention provides an antibody composition comprising ovine antibodies, for use in the prevention or treatment of C. difficile infection wherein the antibodies bind to a C. difficile toxin, and wherein said prevention or treatment is by oral delivery of the antibody composition. Also provided is a pharmaceutical composition of ovine antibodies for oral delivery, which further comprises one or more means for protecting the antibodies from trypsin and/or chymotrypsin and/or stomach acid.

The invention claimed is: 
     
       1. A method for treatment of  C. difficile  infection, comprising orally administering an antibody composition, the antibody composition comprising ovine antibodies that bind to a  C. difficile  toxin,
 wherein the antibodies bind to  C. difficile  Toxin A and to  C. difficile  Toxin B. 
 
     
     
       2. The method of  claim 1 , wherein the antibodies are polyclonal antibodies. 
     
     
       3. The method of  claim 1 , wherein the antibodies bind to  C. difficile  toxins Toxin A, Toxin B, and Binary Toxin. 
     
     
       4. The method of  claim 1 , wherein the  C. difficile  Toxin A is selected from the group consisting of: Toxinotype 0, Toxinotype III and Toxinotype V. 
     
     
       5. The method of  claim 1 , wherein the  C. difficile  Toxin B is selected from the group consisting of: Toxinotype 0, Toxinotype III, Toxinotype V, and Toxinotype VIII. 
     
     
       6. The method of  claim 1 , wherein the antibody composition comprises:
 the ovine antibodies that bind to a  C. difficile  toxin, and 
 at least one means for protecting said antibody composition from trypsin and/or chymotrypsin and/or stomach acid. 
 
     
     
       7. The method of  claim 6 , wherein the at least one means for protecting said antibody composition from trypsin and/or chymotrypsin and/or stomach acid is selected from the group consisting of:
 (a) a polypeptide which binds specifically to and suppresses or inactivates the proteolytic activity of trypsin and/or chymotrypsin; 
 (b) an antibody that binds to trypsin and/or chymotrypsin and suppresses or inactivates the protease activity of said trypsin and/or chymotrypsin; 
 (c) a delivery vehicle selected from a liposome, a microsome, a nanosome, a pellet, a granular matrix, a bead, a microsphere, a nanoparticle formulation, or an aqueous solution; 
 (d) an antacid molecule; 
 (e) a PEGylation moiety covalent attached to one of more of the antibodies. 
 
     
     
       8. The method of  claim 7 , wherein the antibody composition includes the antacid molecule and:
 (a) the polypeptide which binds specifically to and suppresses or inactivates the proteolytic activity of trypsin and/or chymotrypsin; or 
 (b) the antibody that binds to trypsin and/or chymotrypsin and inactivates the protease activity of said trypsin and/or chymotrypsin. 
 
     
     
       9. The method according to  claim 1 , further comprising administering at least one trypsin and/or chymotrypsin inhibitor and/or antacid prior to, simultaneously with, or subsequent to the administering the antibody composition. 
     
     
       10. The method according to  claim 1 , further comprising non-orally administering a second ovine antibody composition wherein said second ovine antibody composition comprises ovine antibodies that bind to a  C. difficile  toxin. 
     
     
       11. The method according to  claim 1 , wherein a subject to be treated is a subject selected from the group consisting of: hospitalized subjects; subjects over 65 years old; subjects receiving broad-range spectrum antibiotics; subjects having previous CDI infection; subjects having close proximity to symptomatic CDI patients; subjects having mild to moderate disease severity; subjects presenting as asymptomatic but considered at high risk of relapse; and subjects having close proximity to CDI outbreak areas or patients. 
     
     
       12. The method of  claim 1 , wherein the antibody composition comprises:
 the ovine antibodies that bind to a  C. difficile  toxin, and 
 an excipient, 
 wherein the excipient provides for colonic delivery of the antibodies from oral administration. 
 
     
     
       13. The method of  claim 12 , wherein the excipient is selected from the group consisting of:
 (a) a polypeptide which binds specifically to and suppresses or inactivates the proteolytic activity of trypsin and/or chymotrypsin; 
 (b) an antibody that binds to trypsin and/or chymotrypsin and suppresses or inactivates the protease activity of trypsin and/or chymotrypsin; 
 (c) a delivery vehicle selected from a liposome, a microsome, and a nanosome; and 
 (d) an antacid molecule. 
 
     
     
       14. A method for preventing at least one clinical symptom of  C. difficile  infection, comprising orally administering an antibody composition, the antibody composition comprising ovine antibodies that bind to a  C. difficile  toxin,
 wherein the antibodies bind to  C. difficile  Toxin A and to  C. difficile  Toxin B. 
 
     
     
       15. The method according to  claim 14 , further comprising administering at least one trypsin and/or chymotrypsin inhibitor and/or antacid prior to, simultaneously with, or subsequent to the administering of the antibody composition. 
     
     
       16. The method according to  claim 14 , further comprising non-orally administering a second ovine antibody composition wherein said second ovine antibody composition comprises ovine antibodies that bind to a  C. difficile  toxin.